Rabbit alveolar macrophages secrete lysosomal enzymes (such as acid phosphatase and beta-glucuronidase), arachidonic acid, and prostaglandins (PGs) during zymosan phagocytosis. The time course of arachidonic acid-PG release did not coincide with particle ingestion, but paralled lysosomal enzyme release, thus suggesting a close association of these two mechanisms. Inhibition of PG synthesis by indomethacin did not inhibit lysosomal enzyme release, suggesting that PGs are not controlling factors for lysosomal enzyme release. The converse, lysosomal enzyme release triggering PG production, remains a possibility, since agents stimulating lysosomal enzyme release (zymosan, bacteria, calcium ion, C5 fragment), also stimulated arachidonic acid PG production. Moreover, drug-induced (dexamethasone, chloroquine) inhibition of lysosomal enzyme release resulted in decrease of arachidonic acid-PG release. However, alveolar macrophages from BCG infected rabbits showed markedly increased intracellular lysosomal enzyme activity and increased lysosomal enzyme release following phagocytosis. In contrast, arachidonic acid and PG release was markedly decreased, even with comparable phagocytosis. Thus, this model demonstrates that lysosomal enzyme release and arachidonic acid-PG production by macrophages are dissociated during delayed hypersensitivity. The possible role of lymphocytes on the suppression of arachidonic acid-PG production by macrophages in delayed hypersensitivity is currently under investigation.